Document Detail

Syndecan-3 modulates food intake by interacting with the melanocortin/AgRP pathway.
MedLine Citation:
PMID:  12851299     Owner:  NLM     Status:  MEDLINE    
Syndecan-3, expressed in the developing nervous system and adult brain, alters feeding behavior through its interaction with the CNS melanocortin system, which provides critical tonic inhibition of both food intake and body adipose stores. A variety of both in vitro and transgenic data supports the hypothesis that syndecan-3 modulates melanocortin activity via syndecan-3 facilitation of agouti-related protein (AgRP), a competitive antagonist of alpha-melanocyte-stimulating hormone (alpha-MSH) at the melanocortin-3 and -4 receptors. Consistent with this hypothesis, mice lacking syndecan-3, which therefore would be predicted to have less effective AgRP, are more sensitive to inhibition of food intake by the melanocortin agonist MTII. Additionally, we took advantage of the fact that syndecan-3 facilitation of AgRP is limited to when it is bound to the cell membrane. Pharmacologic inhibition of the enzyme that cleaves syndecan-3 from the cell membrane leads to increased food intake in fasted rats, which have elevated levels of AgRP. Furthermore, the shedding process appears to be regulated under physiologic conditions, because a putative inhibitor of the shedding process, tissue inhibitor of metalloprotease-3 (TIMP-3), is increased by food deprivation. These observations contribute to the hypothesis that syndecan-3 regulation of melanocortin signaling contributes to the normal control of energy balance. Collectively, the data suggest that the modulation of melanocortin regulation of energy balance by syndecan-3 is modulated by the action of a TIMP-3-sensitive metalloprotease.
Ofer Reizes; Stephen C Benoit; April D Strader; Deborah J Clegg; Shailaja Akunuru; Randy J Seeley
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Annals of the New York Academy of Sciences     Volume:  994     ISSN:  0077-8923     ISO Abbreviation:  Ann. N. Y. Acad. Sci.     Publication Date:  2003 Jun 
Date Detail:
Created Date:  2003-07-09     Completed Date:  2003-08-29     Revised Date:  2011-08-03    
Medline Journal Info:
Nlm Unique ID:  7506858     Medline TA:  Ann N Y Acad Sci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  66-73     Citation Subset:  IM    
Procter Gamble Pharmaceuticals, Inc, Health Care Research Center, Mason, Ohio 45040, USA.
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MeSH Terms
Agouti-Related Protein
Food Deprivation
Intercellular Signaling Peptides and Proteins
Matrix Metalloproteinases / antagonists & inhibitors,  metabolism
Melanocyte-Stimulating Hormones / agonists,  metabolism*
Membrane Glycoproteins / genetics,  metabolism*
Mice, Knockout
Obesity / metabolism
Proteins / metabolism*
Proteoglycans / genetics,  metabolism*
Receptor, Melanocortin, Type 3*
Receptors, Corticotropin / genetics,  metabolism
Receptors, Melanocortin
Tissue Inhibitor of Metalloproteinase-3 / genetics,  metabolism
alpha-MSH / analogs & derivatives*,  metabolism
Reg. No./Substance:
0/AGRP protein, rat; 0/Agouti-Related Protein; 0/Agrp protein, mouse; 0/Intercellular Signaling Peptides and Proteins; 0/Mc3r protein, mouse; 0/Membrane Glycoproteins; 0/Proteins; 0/Proteoglycans; 0/Receptor, Melanocortin, Type 3; 0/Receptors, Corticotropin; 0/Receptors, Melanocortin; 0/Sdc3 protein, mouse; 0/Sdc3 protein, rat; 0/Syndecan-3; 0/Tissue Inhibitor of Metalloproteinase-3; 0/alpha-MSH (4-10)amide, Ac-Nle(4)-cyclo(Asp(5)-Phe(7)-Lys(10))-; 581-05-5/alpha-MSH; 9002-79-3/Melanocyte-Stimulating Hormones; EC 3.4.24.-/Matrix Metalloproteinases

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